Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
This expert opinion report examines the current realities of the cancer pain management landscape and the various factors that hinder optimal pain control in six countries in Southeast Asia, describes ongoing efforts to advance patient care, and discusses approaches for improving cancer pain management. Information was gathered from leading experts in the field of cancer pain management in each country through an initial meeting and subsequent e-mail discussions. Overall, there are vast disparities in cancer pain management practices and access to opioids in the Southeast Asian countries. The experts considered cancer pain as being generally undermanaged. Access to opioids is inadequate in most countries, and opioid use for analgesia remains inadequate in the region. Several system-, physician-, and patient-related barriers to adequate pain relief were identified, including widespread over-regulation of opioid use, shortage of trained health care workers, inadequacies in pain assessment and knowledge about managing pain, and widespread resistance among patients and physicians toward opioid treatment. According to the experts, many of the ongoing initiatives in the Southeast Asian countries are related to educating patients and physicians on cancer pain management and opioid use. Efforts to improve opioid availability and reduce regulatory barriers in the region are limited, and much work is still needed to improve the status of cancer pain management in the region. Enacting necessary change will require recognition of the unique needs and resources of each country and collaboration across interdisciplinary professional teams to improve cancer pain care in this region.
With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia–Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.
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